Trial of second-generation zanamivir shows promise

Aug 1, 2008 (CIDRAP News)  Two pharmaceutical companies that are developing a second-generation version of the inhaled antiviral drug zanamivir (Relenza) reported promising phase 2 results showing that one dose was as effective against influenza as a course of oseltamivir (Tamiflu).

Biota, the Australian company that developed zanamivir, said in a statement yesterday that it is developing the new drug, a long-acting neuraminidase inhibitor (LANI) named CS-8958, through a joint partnership with Japan-based Daiichi-Sankyo.

Neuraminidase inhibitors are used for flu treatment and prevention. The United States and numerous other countries are stockpiling oseltamivir and zanamivir for use against a potential pandemic flu strain. Though the World Health Organization has recommended oseltamivir as the first-line treatment against H5N1 avian influenza, in May British researchers reporting in the journal Nature found that certain mutations in the H5N1 virus that make it resistant to oseltamivir make it vulnerable to zanamivir. They advised nations not to rely on oseltamivir alone when planning their pandemic antiviral stockpiles.

In background materials outlining the company's work on influenza drugs, Biota said the long-acting nature of CS-8958 might allow less frequent dosing and could reduce the storage space needed to stockpile antivirals for future pandemic use.

The phase 2 trial of CS-8958 included "several hundred" adult patients who had confirmed, naturally acquired influenza A or B, according to Biota. The study was designed to assess the drug's safety and efficacy and used fever and symptom resolution as endpoints.

In the double-blind trial, inhaled CS-8958 administered once was "statistically indistinguishable" from 75 mg of oseltamivir given twice a day for 5 days, Biota reported. The company said that in preclinical studies CS-8958 demonstrated efficacy against H5N1 avian influenza, as well as influenza A and B.

The study was conducted according to guidance from Japan's Pharmaceuticals and Medical Devices Agency, according to the statement from Biota. A parallel phase 2 study, performed elsewhere in Asia, addressed dosing. "The results of both trials will be used to support the international regulatory and development program planned for LANI," the company said.

Biota said it and Daiichi-Sankyo were satisfied with the safety, tolerability, and efficacy data for their LANI and that they will use the results to guide a phase 3 trial that will be conducted during the next northern hemisphere influenza season. The phase 3 study will include subjects from locations in Asia, including Japan, Taiwan, Hong Kong, and Korea.

Under a grant from the United States National Institutes of Health, the two companies are at the preclinical development stage for a range of other LANI compounds, Biota said.